tbuckley/cabot-search huggingface dataset:
Comparative Incidence of Diabetes Following Hospital Admission for COVID-19 and Pneumonia: A Cohort Study
Authors: Naomi Holman, Emma Barron, Bob Young, Edward W. Gregg, Kamlesh Khunti, Jonathan Valabhji, Naveed Sattar
Journal: Diabetes Care (2023)

OBJECTIVE The incidence of diabetes may be elevated following coronavirus disease 2019 (COVID-19), but it is unclear whether this is specific to severe acute respiratory syndrome coronavirus 2 infection, associated with shared risk factors for severe COVID-19 and diabetes, and/or a generic risk following illness. RESEARCH DESIGN AND METHODS People admitted to the hospital for COVID-19 and/or pneumonia between 1 April 2020 and 31 August 2020 in England were linked with the National Diabetes Audit to identify incident diabetes after discharge up to 31 March 2021. Comparator cohorts admitted with pneumonia over the same dates in 2017, 2018, and 2019 were followed until 31 March 2018, 31 March 2019, and 31 March 2020, respectively. Poisson regression models were used to calculate adjusted diabetes incidence rates. RESULTS Using the cohort of people discharged from the hospital following a diagnosis of COVID-19 without pneumonia in 2020 as the standard population (incidence rate 16.4 [95% CI 12.8–20.7] per 1,000 person-years), adjusting for age, sex, ethnicity, and deprivation, gave incidence rates of 19.0 (95% CI 13.8–25.6) and 16.6 (95% CI 13.3–20.4) per 1,000 person-years for those admitted for COVID-19 with pneumonia and pneumonia without COVID-19, respectively, in 2020. These rates are not significantly different from those found after hospital admission for pneumonia in 2019, 2018, and 2017, at 13.7 (95% CI 10.8–17.3), 13.8 (95% CI 10.9–17.4), and 14.2 (95% CI 10.9–18.3) per 1,000 person-years, respectively. CONCLUSIONS Our data do not support a clear impact of COVID-19 on the incidence of diabetes compared with risks in several comparator groups, including contemporaneously assessed risks in people hospitalized with pneumonia.
8-Hydroxyquinolylnitrones as multifunctional ligands for the therapy of neurodegenerative diseases
Authors: Damijan Knez, Daniel Diez-Iriepa, Mourad Chioua, Andrea Gottinger, Milica Denic, Fabien Chantegreil, Florian Nachon, Xavier Brazzolotto, Anna Skrzypczak-Wiercioch, Anže Meden, Anja Pišlar, Janko Kos, Simon Žakelj, Jure Stojan, Kinga Sałat, Julia Serrano, Ana Patricia Fernández, Aitana Sánchez-García, Ricardo Martínez-Murillo, Claudia Binda, Francisco López-Muñoz, Stanislav Gobec, José Marco-Contelles
Journal: Acta Pharmaceutica Sinica B (2023)

We describe the development of quinolylnitrones (QNs) as multifunctional ligands inhibiting cholinesterases (ChEs: acetylcholinesterase and butyrylcholinesterase-hBChE) and monoamine oxidases (hMAO-A/B) for the therapy of neurodegenerative diseases. We identified QN 19, a simple, low molecular weight nitrone, that is readily synthesized from commercially available 8-hydroxyquinoline-2-carbaldehyde. Quinolylnitrone 19 has no typical pharmacophoric element to suggest ChE or MAO inhibition, yet unexpectedly showed potent inhibition of hBChE (IC50 = 1.06 ± 0.31 nmol/L) and hMAO-B (IC50 = 4.46 ± 0.18 μmol/L). The crystal structures of 19 with hBChE and hMAO-B provided the structural basis for potent binding, which was further studied by enzyme kinetics. Compound 19 acted as a free radical scavenger and biometal chelator, crossed the blood-brain barrier, was not cytotoxic, and showed neuroprotective properties in a 6-hydroxydopamine cell model of Parkinson's disease. In addition, in vivo studies showed the anti-amnesic effect of 19 in the scopolamine-induced mouse model of AD without adverse effects on motoric function and coordination. Importantly, chronic treatment of double transgenic APPswe-PS1δE9 mice with 19 reduced amyloid plaque load in the hippocampus and cortex of female mice, underscoring the disease-modifying effect of QN 19.
Handcrafted Histological Transformer (H2T): Unsupervised representation of whole slide images
Authors: Quoc Dang Vu, Kashif Rajpoot, Shan E. Ahmed Raza, Nasir Rajpoot
Journal: Medical Image Analysis (2023)

Diagnostic, prognostic and therapeutic decision-making of cancer in pathology clinics can now be carried out based on analysis of multi-gigapixel tissue images, also known as whole-slide images (WSIs). Recently, deep convolutional neural networks (CNNs) have been proposed to derive unsupervised WSI representations; these are attractive as they rely less on expert annotation which is cumbersome. However, a major trade-off is that higher predictive power generally comes at the cost of interpretability, posing a challenge to their clinical use where transparency in decision-making is generally expected. To address this challenge, we present a handcrafted framework based on deep CNN for constructing holistic WSI-level representations. Building on recent findings about the internal working of the Transformer in the domain of natural language processing, we break down its processes and handcraft them into a more transparent framework that we term as the Handcrafted Histological Transformer or H2T. Based on our experiments involving various datasets consisting of a total of 10,042 WSIs, the results demonstrate that H2T based holistic WSI-level representations offer competitive performance compared to recent state-of-the-art methods and can be readily utilized for various downstream analysis tasks. Finally, our results demonstrate that the H2T framework can be up to 14 times faster than the Transformer models.
Diffusion MRI data analysis assisted by deep learning synthesized anatomical images (DeepAnat)
Authors: Ziyu Li, Qiuyun Fan, Berkin Bilgic, Guangzhi Wang, Wenchuan Wu, Jonathan R. Polimeni, Karla L. Miller, Susie Y. Huang, Qiyuan Tian
Journal: Medical Image Analysis (2023)

Diffusion MRI is a useful neuroimaging tool for non-invasive mapping of human brain microstructure and structural connections. The analysis of diffusion MRI data often requires brain segmentation, including volumetric segmentation and cerebral cortical surfaces, from additional high-resolution T
Single-cell transcriptomic analyses provide insights into the cellular origins and drivers of brain metastasis from lung adenocarcinoma
Authors: Zihao Wang, Yaning Wang, Mengqi Chang, Yuekun Wang, Peng Liu, Jianqiang Wu, Guige Wang, Xiaoyue Tang, Xiangyi Hui, Penghao Liu, Xiaopeng Guo, Bing Xing, Yu Wang, Zhijun Han, Wenbin Ma
Journal: Neuro-Oncology (2023)

Abstract Background Brain metastasis (BM) is the most common intracranial malignancy causing significant mortality, and lung cancer is the most common origin of BM. However, the cellular origins and drivers of BM from lung adenocarcinoma (LUAD) have yet to be defined. Methods The cellular constitutions were characterized by single-cell transcriptomic profiles of 11 LUAD primary tumor (PT) and 10 BM samples (GSE131907). Copy number variation (CNV) and clonality analysis were applied to illustrate the cellular origins of BM tumors. Brain metastasis-associated epithelial cells (BMAECs) were identified by pseudotime trajectory analysis. By using machine-learning algorithms, we developed the BM-index representing the relative abundance of BMAECs in the bulk RNA-seq data indicating a high risk of BM. Therapeutic drugs targeting BMAECs were predicted based on the drug sensitivity data of cancer cell lines. Results Differences in macrophages and T cells between PTs and BMs were investigated by single-cell RNA (scRNA) and immunohistochemistry and immunofluorescence data. CNV analysis demonstrated BM was derived from subclones of PT with a gain of chromosome 7. We then identified BMAECs and their biomarker, S100A9. Immunofluorescence indicated strong correlations of BMAECs with metastasis and prognosis evaluated by the paired PT and BM samples from Peking Union Medical College Hospital. We further evaluated the clinical significance of the BM-index and identified 7 drugs that potentially target BMAECs. Conclusions This study clarified possible cellular origins and drivers of metastatic LUAD at the single-cell level and laid a foundation for early detection of LUAD patients with a high risk of BM.
Amphiphilic Dendrimer Doping Enhanced pH‐Sensitivity of Liposomal Vesicle for Effective Co‐delivery toward Synergistic Ferroptosis–Apoptosis Therapy of Hepatocellular Carcinoma
Authors: Yanhong Su, Zhao Zhang, Leo Tsz On Lee, Ling Peng, Ligong Lu, Xu He, Xuanjun Zhang
Journal: Advanced Healthcare Materials (2023)

Ferroptosis, characterized by the accumulation of reactive oxygen species and lipid peroxides, has emerged as an attractive strategy to reverse drug resistance. Of particular interest is the ferroptosis-apoptosis combination therapy for cancer treatment. Herein, a nanoplatform is reported for effective co-delivery of the anticancer drug sorafenib (S) and the ferroptosis inducer hemin (H), toward synergistic ferroptosis-apoptosis therapy of advanced hepatocellular carcinoma (HCC) as a proof-of-concept study. Liposome is an excellent delivery system; however, it is not sufficiently responsive to the acidic tumor microenvironment (TME) for tumor-targeted drug delivery. The pH-sensitive vesicles are therefore developed (SH-AD-L) by incorporating amphiphilic dendrimers (AD) into liposomes for controlled and pH-stimulated release of sorafenib and hemin in the acidic TME, thanks to the protonation of numerous amine functionalities in AD. Importantly, SH-AD-L not only blocked glutathione synthesis to disrupt the antioxidant system, but also increased intracellular Fe2+ and ·OH concentrations to amplify oxidative stress, both of which contribute to enhanced ferroptosis. Remarkably, high levels of ·OH also augmented sorafenib-mediated apoptosis in tumor cells. This study demonstrates the efficacy of ferroptosis-apoptosis combination therapy, as well as the promise of the AD-doped TME-responsive vesicles for drug delivery in combination therapy to treat advanced HCC.
Preclinical and clinical evidence for suppression of alcohol intake by apremilast
Authors: Kolter B. Grigsby, Regina A. Mangieri, Amanda J. Roberts, Marcelo F. Lopez, Evan J. Firsick, Kayla G. Townsley, Alan Beneze, Jessica Bess, Toby K. Eisenstein, Joseph J. Meissler, John M. Light, Jenny Miller, Susan Quello, Farhad Shadan, Michael Skinner, Heather C. Aziz, Pamela Metten, Richard A. Morrisett, John C. Crabbe, Marisa Roberto, Howard C. Becker, Barbara J. Mason, Angela R. Ozburn
Journal: Journal of Clinical Investigation (2023)

Treatment options for alcohol use disorders (AUDs) have minimally advanced since 2004, while the annual deaths and economic toll have increased alarmingly. Phosphodiesterase type 4 (PDE4) is associated with alcohol and nicotine dependence. PDE4 inhibitors were identified as a potential AUD treatment using a bioinformatics approach. We prioritized a newer PDE4 inhibitor, apremilast, as ideal for repurposing (i.e., FDA approved for psoriasis, low incidence of adverse events, excellent safety profile) and tested it using multiple animal strains and models, as well as in a human phase IIa study. We found that apremilast reduced binge-like alcohol intake and behavioral measures of alcohol motivation in mouse models of genetic risk for drinking to intoxication. Apremilast also reduced excessive alcohol drinking in models of stress-facilitated drinking and alcohol dependence. Using site-directed drug infusions and electrophysiology, we uncovered that apremilast may act to lessen drinking in mice by increasing neural activity in the nucleus accumbens, a key brain region in the regulation of alcohol intake. Importantly, apremilast (90 mg/d) reduced excessive drinking in non-treatment-seeking individuals with AUD in a double-blind, placebo-controlled study. These results demonstrate that apremilast suppresses excessive alcohol drinking across the spectrum of AUD severity.
Lost in translation: understanding the experience of atopic eczema among non-English-speaking families
Authors: Korey Capozza
Journal: British Journal of Dermatology (2023)

https://doi.org/10.1093/bjd/ljad015 Atopic eczema (‘eczema’) is a condition whose impacts are largely hidden from view. Clinicians often focus on the visible signs of eczema, such as the redness or dryness of the skin, while patients report that the most troublesome symptoms are the invisible ones: itch and exhaustion caused by sleep loss.1 Eczema can have a profound and wide-ranging impact on quality of life (QoL) by eroding mental health, social activities and finances; however, these impacts cannot be assessed through a physical medical examination.2,3 The measurement of QoL is therefore critical to determining the severity of eczema and understanding the patient experience. While many validated QoL instruments already exist for gauging such impacts in patients with eczema and their caregivers, few have been validated in minority populations, which remains a major shortcoming. The original article by Tawfik et al. provides valuable insight into the limitations of our current approaches to assessing QoL in non-English-speaking immigrant groups, particularly patients and families of Bangladeshi origin living in East London.4
Type 2 diabetes candidate genes, including PAX5, cause impaired insulin secretion in human pancreatic islets
Authors: Karl Bacos, Alexander Perfilyev, Alexandros Karagiannopoulos, Elaine Cowan, Jones K. Ofori, Ludivine Bertonnier-Brouty, Tina Rönn, Andreas Lindqvist, Cheng Luan, Sabrina Ruhrmann, Mtakai Ngara, Åsa Nilsson, Sevda Gheibi, Claire L. Lyons, Jens O. Lagerstedt, Mohammad Barghouth, Jonathan L.S. Esguerra, Petr Volkov, Malin Fex, Hindrik Mulder, Nils Wierup, Ulrika Krus, Isabella Artner, Lena Eliasson, Rashmi B. Prasad, Luis Rodrigo Cataldo, Charlotte Ling
Journal: Journal of Clinical Investigation (2023)

Type 2 diabetes (T2D) is caused by insufficient insulin secretion from pancreatic β cells. To identify candidate genes contributing to T2D pathophysiology, we studied human pancreatic islets from approximately 300 individuals. We found 395 differentially expressed genes (DEGs) in islets from individuals with T2D, including, to our knowledge, novel (OPRD1, PAX5, TET1) and previously identified (CHL1, GLRA1, IAPP) candidates. A third of the identified expression changes in islets may predispose to diabetes, as expression of these genes associated with HbA1c in individuals not previously diagnosed with T2D. Most DEGs were expressed in human β cells, based on single-cell RNA-Seq data. Additionally, DEGs displayed alterations in open chromatin and associated with T2D SNPs. Mouse KO strains demonstrated that the identified T2D-associated candidate genes regulate glucose homeostasis and body composition in vivo. Functional validation showed that mimicking T2D-associated changes for OPRD1, PAX5, and SLC2A2 impaired insulin secretion. Impairments in Pax5-overexpressing β cells were due to severe mitochondrial dysfunction. Finally, we discovered PAX5 as a potential transcriptional regulator of many T2D-associated DEGs in human islets. Overall, we have identified molecular alterations in human pancreatic islets that contribute to β cell dysfunction in T2D pathophysiology.
Active Remodeling of Capillary Endothelium via Cancer Cell–Derived MMP9 Promotes Metastatic Brain Colonization
Authors: Matthia A. Karreman, Alexander T. Bauer, Gergely Solecki, Anna S. Berghoff, Chanté D. Mayer, Katharina Frey, Nils Hebach, Manuel J. Feinauer, Nicole L. Schieber, Cedric Tehranian, Luc Mercier, Mahak Singhal, Varun Venkataramani, Marc C. Schubert, Daniel Hinze, Michael Hölzel, Iris Helfrich, Dirk Schadendorf, Stefan W. Schneider, Dana Westphal, Hellmut G. Augustin, Jacky G. Goetz, Yannick Schwab, Wolfgang Wick, Frank Winkler
Journal: Cancer Research (2023)

Crossing the blood-brain barrier is a crucial, rate-limiting step of brain metastasis. Understanding of the mechanisms of cancer cell extravasation from brain microcapillaries is limited as the underlying cellular and molecular processes cannot be adequately investigated using in vitro models and endpoint in vivo experiments. Using ultrastructural and functional imaging, we demonstrate that dynamic changes of activated brain microcapillaries promote the mandatory first steps of brain colonization. Successful extravasation of arrested cancer cells occurred when adjacent capillary endothelial cells (EC) entered into a distinct remodeling process. After extravasation, capillary loops were formed, which was characteristic of aggressive metastatic growth. Upon cancer cell arrest in brain microcapillaries, matrix-metalloprotease 9 (MMP9) was expressed. Inhibition of MMP2/9 and genetic perturbation of MMP9 in cancer cells, but not the host, reduced EC projections, extravasation, and brain metastasis outgrowth. These findings establish an active role of ECs in the process of cancer cell extravasation, facilitated by cross-talk between the two cell types. This extends our understanding of how host cells can contribute to brain metastasis formation and how to prevent it.
Reasons for Receiving or Not Receiving Bivalent COVID-19 Booster Vaccinations Among Adults — United States, November 1–December 10, 2022
Authors: Alyssa H. Sinclair, Morgan K. Taylor, Joshua S. Weitz, Stephen J. Beckett, Gregory R. Samanez-Larkin
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Bivalent COVID-19 booster vaccines, developed to protect against both ancestral and Omicron BA.4/BA.5 variants, are recommended to increase protection against SARS-CoV-2 infection and severe disease* (1,2). However, relatively few eligible U.S. adults have received a bivalent booster dose (3), and reasons for low coverage are unclear. An opt-in Internet survey of 1,200 COVID-19-vaccinated U.S. adults was conducted to assess reasons for receiving or not receiving a bivalent booster dose. Participants could select multiple reasons from a list of suggested reasons to report why they had or had not received a bivalent booster dose. The most common reasons cited for not receiving the bivalent booster dose were lack of awareness of eligibility for vaccination (23.2%) or of vaccine availability (19.3%), and perceived immunity against infection (18.9%). After viewing information about eligibility and availability, 67.8% of participants who had not received the bivalent booster dose indicated that they planned to do so; in a follow-up survey 1 month later, 28.6% of these participants reported having received the dose. Among those who had planned to receive the booster dose but had not yet done so, 82.6% still intended to do so. Participants who had still not received the booster dose most commonly reported being too busy to get vaccinated (35.6%). To help increase bivalent booster dose coverage, health care and public health professionals should use evidence-based strategies to convey information about booster vaccination recommendations and waning immunity (4), while also working to increase convenient access.
Reply to Sandra Patricia García Nader, Sebastián Peña Rodríguez, and Cesar Alejandro Diaz Ritter’s Letter to the Editor re: Farnoosh Nik-Ahd, Andrew Jarjour, Jane Figueiredo, et al. Prostate-specific Antigen Screening in Transgender Patients. Eur Urol. 2023;83:48–54
Authors: Farnoosh Nik-Ahd, Matthew R. Cooperberg, Stephen J. Freedland
Journal: European Urology (2023)
Corrigendum to ‘Utility of plasma cell-free DNA next-generation sequencing for diagnosis of infectious diseases in patients with hematological disorders’ [Journal of Infection Volume 86 Issue 1 (2023) pages 14–23]
Authors: Chunhui Xu, Xin Chen, Guoqing Zhu, Huiming Yi, Shulian Chen, Yuetian Yu, Erlie Jiang, Yizhou Zheng, Fengkui Zhang, Jianxiang Wang, Sizhou Feng
Journal: Journal of Infection (2023)
<i>Notes from the Field</i>: Follow-Up Assessment 1 Year After a Chemical Exposure Investigation — Winnebago County, Illinois, July–August 2022
Authors: Ahlia Sekkarie, Peter DeJonge, Sandra Martell, Sarah Patrick, Motria Caudill, D. Kevin Horton, Maureen Orr, Stacey Konkle
Journal: MMWR Morbidity and Mortality Weekly Report (2023)
Substance Use Among Persons with Syphilis During Pregnancy — Arizona and Georgia, 2018–2021
Authors: Jeffrey M. Carlson, Ayzsa Tannis, Kate R. Woodworth, Megan R. Reynolds, Neha Shinde, Breanne Anderson, Keivon Hobeheidar, Aisha Praag, Kristen Campbell, Cynthia Carpentieri, Teri Willabus, Elizabeth Burkhardt, Elizabeth Torrone, Kevin P. O’Callaghan, Kathryn Miele, Dana Meaney-Delman, Suzanne M. Gilboa, Emily O’Malley Olsen, Van T. Tong
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Despite universal prenatal syphilis screening recommendations and availability of effective antibiotic treatment, syphilis prevalence during pregnancy and the incidence of congenital syphilis have continued to increase in the United States (1,2). Concurrent increases in methamphetamine, injection drug, and heroin use have been described in women with syphilis (3). CDC used data on births that occurred during January 1, 2018-December 31, 2021, from two states (Arizona and Georgia) that participate in the Surveillance for Emerging Threats to Pregnant People and Infants Network (SET-NET) to describe the prevalence of substance use among pregnant persons with syphilis by congenital syphilis pregnancy outcome (defined as delivery of a stillborn or live-born infant meeting the surveillance case definition for probable or confirmed congenital syphilis). The prevalence of substance use (e.g., tobacco, alcohol, cannabis, illicit use of opioids, and other illicit, nonprescription substances) in persons with a congenital syphilis pregnancy outcome (48.1%) was nearly double that among those with a noncongenital syphilis pregnancy outcome (24.6%). Persons with a congenital syphilis pregnancy outcome were six times as likely to report illicit use of opioids and four times as likely to report using other illicit, nonprescription substances during pregnancy than were persons with a noncongenital syphilis pregnancy outcome. Approximately one half of persons who used substances during pregnancy and had a congenital syphilis pregnancy outcome had late or no prenatal care. Tailored interventions should address barriers and facilitators to accessing screening and treatment for syphilis among persons who use substances. The need for syphilis screening and treatment should be addressed at any health care encounter during pregnancy, especially among persons who use substances.